The major structures of the eye are the sclera, cornea, iris, lens, vitreous, retina, and optic nerve. The function of the lens, which is located behind the iris, is to focus light onto the retina. The lens is mostly composed of water and proteins. The structure of the lens and the arrangement of the protein lens fibers allow light to pass through and focus on the retina, which senses the light and sends visual signals to the brain via the optic nerve. The transparency of the lens is essential for normal vision.
A cataract is a clouding or development of an opaque area in the lens. Most cataracts form as part of the aging process, but some are associated with congenital or systemic pathological conditions and others are related to ocular trauma. Cataracts are formed by the clumping of the proteins in the lens and the opacification that ensues, which hinders light transmission and normal vision.
At present, the only effective way to treat cataracts is to surgically remove the opaque lens. It is estimated that about 2.3 million cataract surgeries were performed in the United States in 2004, and the number of such procedures has been shown to increase by about 3% per year (Market Scope).
Currently, there are several operative procedures for removing cataracts: extracapsular cataract extraction, intracapsular cataract extraction, and phacoemulsification. In extracapsular cataract extraction, a large bulk of cataractus material is expressed from the eye through a moderately large incision. In contrast, in intracapsular cataract extraction, the entire cataract is removed from the eye in one piece.
Currently, phacoemulsification, a form of extracapsular cataract surgery, is the most common method of cataract removal in the United States and in many Western countries. In phacoemulsification, which is performed through a small incision, the cataractus lens material is ground up by ultrasonic energy and aspirated from the eye by suction. Most often, an intraocular lens is inserted in the patient's eye at the time of the cataract removal. This synthetic lens has clear optics and replaces the removed cataractus lens material.
While phacoemulsification and other forms of cataract surgery are considered to be safe surgical techniques, corneal endothelial damage can still be a serious complication. Excessive damage to the corneal endothelium can lead to irreversible decompensation of the cornea which results in corneal swelling (bullous keratopathy), pain, and loss of vision. Corneal, damage can be caused by shock wave injury, fluid flow turbulence injury, thermal injury, free-radical formation, and increased intraocular pressure (Takahashi et al., Arch Ophthalmology; 120:1348-1352 (2002); Cameron et al., J Cataract Refract Surg.; 27:463-470 (2001); Shimmuara et al., Invest Ophthalmol Vis Sci.; 33:2904-2907 (1992); Holst et al., Current Eye Research; 12:359-365 (1993)).
During phacoemulsification, hydroxyl radicals and hydrogen atoms are formed when the ultrasound energy in aqueous solution induces acoustic cavitations that cause gas bubbles to collapse, leading to the thermal dissociation of water and vapor into hydroxyl radicals and hydrogen atoms (Takahashi et al., Arch Opthalmology; 120:1348-1352 (2002); Cameron et al., J Cataract Refract Surg.; 27:463-470 (2001)). Such free radicals can inhibit the function of important cellular proteins, such as lactate dehydrogenase and creatine kinase, and induce strand breaks in DNA, resulting in endothelial damage (Miura, et al., Biochemistry & Molecular Biology International; 125-133 (1993); Hiramoto, et al., Biol Pharm Bull.; 558-563 (1996)).
Most Ophthalmic Viscosurgical Devices (OVDs) are polysaccharides of hyaluronic acid which are used during cataract surgery. OVDs protect and maintain the space and stability of the ocular structures during the surgical procedure (Buratto et al., Viscoelastics in Ophthalmic Surgery, Slack Inc Publishings, (2000)). However despite their advantages, the use of OVDs has been correlated with significant increases in postoperative intraocular pressure (Mac Rae et al., Am J Ophthalmol; 95:332-341 (1983), Glasser et al., Arch Ophthalmol.; 104:18198-1824 (1986); Raitta et al., Acta Ophthalmol.; 66:544-551 (1988)), which can lead to ocular damage. It has been hypothesized that the retained hyaluronic acid and other material from the OVDs block the outflow facility of the aqueous humor, resulting in an increase in intraocular pressure (Berson et al., Am J Ophthalmol.; 95: 668-672 (1983)).
Phacoemulsification and other cataract extracapsular removal procedures require the use of a balanced salt solution which is irrigated into the anterior chamber of the eye during the procedure. This irrigating solution maintains the shape of the eye, keeps the ultrasonic tip of the phacoemulsification unit, which is vibrating at approximately 40,000 cycles per second, cool, and assists in the elimination of cataractus lens particles in all types of extracapsular cataract surgery. During surgery, the irrigating solution is constantly flowed into the eye and aspirated out, thus maintaining an equilibrium pressure in the eye. More specifically, the tip of the phacoemulsification unit is connected via tubing to a bottle of balanced salt solution. The solution thus flows through the tip. Simultaneously, the center of the tip provides suction to remove the cataract material and salt solution, maintaining equilibrium. The flow is controlled via a foot pedal which is operated by the surgeon. It is common to leave some of the irrigating solution in the eye at the conclusion of the surgical procedure to maintain the shape of the eye.
Some commercially available intraocular irrigating solutions also help to protect corneal endothelial cells. For example, Balanced Salt Solution Plus (BSS PLUS®) (Alcon Laboratories, Inc., Fort Worth, Tex.) is an intraocular irrigating solution that has been demonstrated to reduce corneal endothelium damage during phacoemulsification (Glasser, et al., Am J Ophthalmol.; 99:321-328 (1985)). BSS PLUS® contains, in addition to various salts, glutathione, sodium bicarbonate, and dextrose. Glutathione is a natural antioxidant that serves as a free-radical scavenger and has been demonstrated to help protect the corneal endothelium and maintain corneal transparency (Edelhauser et al., Arch. Ophthalmol.; 96:516-520 (1978); Araie et al., Invest Opth Vis Sci.; 29:1884-1887 (1985); Whikehart et al., Current Eye Res.; 1:451-5 (1981)). Sodium bicarbonate functions as a buffer solution and dextrose acts as an energy source that can help maintain proper metabolism (Hodson et al., J. Physiol.; 263:563-77 (1976); Hull et al., Invest Ophthalmol Vis Sci.; 16:883-892 (1977); Barfort et al., Exp Eye Res.; 19:11-19 (1974)).
Many surgeons prefer to use BSS PLUS® because it is, at present, the only intraocular irrigating solution which has undergone appropriate clinical evaluation for endothelial protection. However at a price range of $50-$60 per 500 ml bottle (with only about:40% of the bottle being utilized), the use of BSS PLUS® is very costly to the surgeon and patient care. The unused, discarded BSS PLUS® results in a loss of about $30 per procedure or $40,000 per year or more for an average surgical center.
A post-operative intraocular pressure rise during the first twenty-four hours after cataract surgery is common. Such a pressure rise is especially common when OVDs are used, since some of the OVD which is not aspirated from the eye blocks the trabecular meshwork. While post-operative pressure rises may also occur in the absence of OVDs, they are typically not as severe. For a typical patient, a normal intraocular pressure level is less than about 20 mm Hg gauge, and usually about 10 to about 18 mm Hg gauge. Following surgery, intraocular pressures as high as 40 mm Hg gauge are observed in some cases. In some patients, particularly those suffering from advanced glaucoma, intraocular pressure rises may be disastrous and result in visual loss. Specifically, the high pressure compromises circulation to the optic nerve, with subsequent death of retinal cells.
Current methods for relieving post-operative pressure increases in the eye include various types of eye drops, such as beta-adrenergic blocking agents, sympathomimetic agents, miotics, alpha II selective agents, carbonic anhydrase inhibitors, and prostaglandin agents, as well as systemic carbonic anhydrase inhibitors. Tables listing some of these agents appear in the Physician's Desk Reference for Ophthalmology 2006.
Such methods for relieving elevated intraocular pressure are often undesirable because of the side effects of many of these drugs. For example, systemic carbonic anhydrase inhibitors can cause lethargy and, in some instances, disorientation. Beta-blocker medications are contraindicated in patients with breathing problems or slow heart rates. Sympathomimetic drugs can cause an increase in blood pressure. Parasympathomimetic drugs can be associated with retinal detachments in eyes with peripheral retinal and retinovascular diseases. The above medications all work to lower intraocular pressure by either decreasing aqueous humor formation or increasing the amount of aqueous humor outflow (removal) from the anterior chamber. In some instances, if significant amounts of hyaluronic acid or a similar viscoelastic agent which is added during surgery are left in the eye and medications are not effective in lowering the intraocular pressure, it may be necessary to surgically aspirate them by performing a second surgical procedure which removes the retained OVD or other material. However, aspirating the remaining viscoelastic agent from a patient's anterior chamber subjects the patient to an additional operative procedure.
U.S. Pat. No. 6,745,776 of Applicant is directed to a method for reducing postoperative intraocular pressure in an eye. The method involves injecting a combination of hyaluronidase and hyaluronic acid into the anterior chamber of the eye at the appropriate time during an operative procedure. The hyaluronidase which is administered with the hyaluronic acid is provided in an amount effective to reduce the intraocular pressure to substantially pre-operative levels. However, such a method is performed only in conjunction with the administration of hyaluronic acid during surgery.
It would thus be desirable to find a better method of controlling post-operative intraocular pressure increases which would be effective and applicable in all types of ophthalmic surgeries. Preferably, such a method would also prevent endothelial cell damage by preventing such post-operative intraocular pressure rises.